System and method for managing crystallization process in a process control plant

This application claims priority to PCT Application No. PCT/EP2019/081829, having a filing date of Nov. 19, 2019, the entire contents of which is hereby incorporated by reference.

The following relates to a field of process control systems, and more particularly relates to system and method for managing crystallization process in process plants.

Crystallization is one of a key unit operation in pharmaceutical and chemical industry. Cooling type crystallization is a thermal separation and purification process which yields a solid product from a solution. This solid is pure API crystals. The process of cooling involves use of different utilities for cooling purpose. These utilities are circulated in a jacket/coils of reactor. Some common utilities are hot water, cooling tower water, chilled water and brine. In the process of cooling, it is essential to meet non equilibrium conditions which acts as a driving force for the cooling process. To establish this non equilibrium conditions, evaporation of solvent or temperature reduction (cooling) methods are more frequently employed in the process control industry. The key factors in design of any thermal separation process, such as cooling type crystallization are thermodynamics and kinetics of process control system in process. Thermodynamics of the process control system defines outcomes of the process control system that can be achieved and kinetics of the process control system defines a time scale to achieve such outcomes. This defines and controls crystallization process.

Two processes are important in crystallization, namely process of nucleation and process of crystal growth. Both of these processes are dependent on large number of process parameters that in many cases may be poorly defined. For example, whenever suspensions of crystals in solutions are involved, process parameters such as attrition and agglomeration are considered. These crystals possess an internal structure, external shape and consequently finite size or size distribution in case of quantity of crystals. These parameters define many bulk properties of a given crystalline material such as dissolution rate, bioavailability, color, flow properties etc. A number of factors have to be accounted for when determining solubility of the solvent. First and foremost, it is indeed important to ensure if the solution is in equilibrium condition. At this point, it is important to stress that crystallization is a non-equilibrium process. The value of understanding the equilibrium properties of the solution lies in the fact that they dictate the operating conditions for the crystallization process. The driving force required for nucleation and crystal growth is the level of super saturation in the solution. This means that the crystallization can only occur at solution compositions where the amount of solute exceeds the solubility limit. Such solutions are called super saturated solutions. Also, the region of phase space where supersaturated solution exists is known as metastable zone. To control the nucleation and crystal growth, it is important to operate crystallizer precisely within the metastable zone. The crystal growth rates not only depend upon the temperature, pressure and composition of mother liquor but also on parameters such as super saturation. It is important to control super saturation and one of the important factors that control the super saturation is proper cooling rate. It becomes necessary to control the cooling rate in order to control the rate of nucleation and crystal growth. If the cooling rate is not maintained at the desired value, then there exists below problems:

Currently crystallizers are operated manually or automated with advanced Proportional, Integral, Derivative (PID) logic. Many times, crystallizers are operated using either single or multi-fluid cooling utilities. The utilities are supplied from common source catering many crystallizer reactors. The capacity of the common source may always not be sufficient to operate all crystallizer reactors at the same time. This leads to occurrence of process complexities such as:

Conventionally, there are certain major process disturbances which are not accounted for during the cooling process. These include:

All these un-predicted, un-controlled process disturbances are not being taken care either manually, or through a control system, or through a Proportional, Integral, Derivative (PID) logic. This affects the process parameters as mentioned above. Due to above factors, the process parameters influencing the cooling process are compromised resulting in inconsistency, non-regulatory compliance, loss of percentage yield, particle size distribution and crystal morphology. This is a huge process challenge and requires immediate remedy.

In light of the above, there exists a need for providing a method and system for effectively and accurately managing cooling control process in a process industry.

An aspect relates to a method and system for automatically operating reactor units in a process plant to accurately determine cooling control curve within metastable zone to generate nuclei, control nuclei generation and then nuclei to come together to form crystal with desired morphology.

The aspect of the disclosure is achieved by a method for managing crystallization process in a process control plant. The method comprises capturing process parameters of an operating reactor unit in a process control plant. The process parameters are captured via one or more sensing unit. The process parameters comprises cooling rate, utility management, super saturation, temperature of the operating reactor unit, properties of utilities, parameters related to utility flow management, smart positioner properties, and the like and wherein the utility flow management comprises managing desired utility at desired temperature, at desired time, and at desired flow. The one or more sensing unit comprises one or more temperature sensors external to the operating reactor unit for measuring utility jacket inlet temperature and jacket outlet temperature, one or more temperature sensor deployed internal to the operating reactor unit for measuring crystallization mass temperature, one or more flow meters for measuring utility flow rate, a smart positioner with an automatic control valve for positioning a control element and controlling flow of utility into the operating reactor unit.

Further, the method comprises predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the operating reactor unit. Furthermore, the method comprises controlling process control loop associated with the operating reactor unit based on the desired process parameters and the first set of parameters.

In an embodiment, in predicting the desired process parameters based on the first set of parameters and the captured process parameters, the method comprises computing actual instantaneous cooling rate required for the operating reactor unit based on a second set of parameters associated with the operating reactor unit. Further, the method comprises computing desired cooling rate through utility(s) based on the actual instantaneous cooling rate required and based on a third set of parameters. Also, the method comprises computing desired utility flow for the operating reactor unit based on the computed actual instantaneous cooling rate required, the desired cooling rate, the process dynamics, a Logarithmic Mean Temperature Difference (LMTD) value, a pinch temperature value and Reynold number analysis.

In an embodiment, in computing the actual instantaneous cooling rate required for the operating reactor unit based on the second set of parameters associated with the operating reactor unit, the method comprises determining second set of parameters associated with the operating reactor unit using the one or more sensing unit. The second set of parameters comprises crystallization mass, specific heat of crystallization mass, initial crystallization mass temperature, final crystallization mass temperature, initial batch time, final batch time, instantaneous crystallization mass temperature, instantaneous batch time, and time lapsed versus actual step change time.

In another embodiment, in computing the desired cooling rate through the utility(s) based on the actual instantaneous cooling rate required and based on the third set of parameters, the method comprises determining the third set of parameters associated with the operating reactor unit. The third set of parameters comprises actual flow of utility and specific heat of utility being used in the operating reactor unit.

In another embodiment, the pinch temperature value is computed by generating a pinch curve depicting a temperature difference between instantaneous crystallization mass temperature and utility jacket outlet temperature. Further, the method comprises determining whether the temperature difference is dropped below a predefined threshold value. Also, the method comprises identifying the pinch temperature value corresponding to the determined temperature difference which is dropped below the predefined threshold value.

In yet another embodiment, the logarithmic mean temperature difference value is computed by determining logarithmic mean temperature difference between a) initial crystallization mass temperature and utility jacket outlet temperature, and b) crystallization mass temperature and utility jacket inlet temperature.

In still another embodiment, in predicting the desired process parameters based on the first set of parameters and the captured process parameters, the method comprises determining flow of subsequent utility into the operating reactor unit based on the actual instantaneous cooling rate required when purging is complete, instantaneous crystallization mass temperature and the logarithmic mean temperature difference value.

In an embodiment, in controlling the process control loop associated with the operating reactor unit based on the desired process parameters and the first set of parameters, the method comprises determining actual flow of utility into the operating reactor unit based on the captured process parameters. Further, the method comprises comparing the desired utility flow for the operating reactor unit with the actual flow of utility to determine a utility flow error value. Furthermore, the method comprises controlling the process control loop associated with the operating reactor unit based on the utility flow error value.

In an embodiment, controlling the process control loop associated with the operating reactor unit based on the utility flow error value, the method comprises generating a control signal indicating a change of position of a smart positioner associated with the operating reactor unit based on the utility flow error value. Further, the method comprises determining current position of the smart positioner using the captured process parameters. Further, the method comprises transmitting the generated control signal to the smart positioner via a control system. The method further comprises determining hysteresis value associated with the smart positioner. Also, the method comprises repositioning the smart positioner based on the transmitted control signal, wherein the repositioning of the smart positioner rectifies the utility flow error value to zero value.

In yet another embodiment, in controlling the process control loop associated with the operating reactor unit based on the desired process parameters and the first set of parameters, the method comprises determining loop control mode of selection of a control system. The loop control mode of selection comprises at least one of a Proportional, Integral, Derivative (PID) mode or an advanced cooling control (or auto) mode. Further, the method comprises determining desired cooling rate slope of the operating reactor unit based on pinch temperature and time factor, if the loop control mode of selection is in auto mode. Furthermore, the method comprises comparing the determined desired cooling rate slope with actual cooling rate slope. Also, the method comprises controlling the process control loop associated with the operating reactor unit based on the comparison.

The aspect of the present disclosure is also achieved by a process plant. The process plant comprises one or more operating reactor unit. The one or more operating reactor unit comprises an enclosure capable of yielding a solid product from a solution through a crystallization process. The enclosure comprises a crystallization mass and a mass temperature sensor for measuring temperature of the crystallization mass. Further, the process plant comprises one or more external temperature sensors for measuring utility jacket inlet and outlet temperature and steam inlet temperature. Furthermore, the process plant comprises one or more flow meters for measuring one or more utility flow rate with respect to the one or more operating reactor unit and measuring steam flow rate. Also, the process plant comprises one or more automatic control valves comprising a smart positioner for positioning a control element and controlling flow of utility into the one or more operating reactor unit. Additionally, the process plant comprises a control system coupled to the one or more automatic control valves, one or more flow meters, the mass temperature sensor and the one or more external temperature sensors.

The control system is capable of capturing process parameters of the one or more operating reactor unit. The process parameters are captured via the one or more flow meters, the mass temperature sensor and the one or more external temperature sensors. Further, the control system is capable of predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the one or more operating reactor unit. Furthermore, the control system is capable of controlling process control loop associated with the one or more operating reactor unit based on the desired process parameters and the first set of parameters.

The control system further comprises a control unit for monitoring and controlling the process control loop associated with the one or more operating reactor unit. Also, the control system comprises a remote input/output box for transmitting control signals to the one or more flow meters, the mass temperature sensor and the one or more external temperature sensors.

The control system is further capable of analyzing the first set of parameters comprising information related to process dynamics and process disturbances associated with the one or more operating reactor unit.

The control system is further capable of periodically monitoring the process control loop associated with the one or more operating reactor unit.

The object of the present disclosure is further achieved by a control unit. The control unit comprises a processor and a memory coupled to the processor. The memory comprises a process control module stored in the form of machine-readable instructions and executable by the processor. The process control module is capable of capturing process parameters of an operating reactor unit in a process plant. The process parameters are captured via one or more sensing unit. Further, the process control module is capable of predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the operating reactor unit. The process control module is further capable of controlling process control loop associated with the operating reactor unit based on the desired process parameters and the first set of parameters.

Further, the process control module is capable of storing the captured process parameters, desired critical parameters, first set of parameters, second set of parameters, and third set of parameters.

The above-mentioned and other features of the disclosure will now be addressed with reference to the accompanying drawings of the present disclosure. The illustrated embodiments are intended to illustrate, but not limit the disclosure.

Various embodiments are described with reference to the drawings, wherein like reference numerals are used to refer the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for the purpose of explanation, numerous specific details are set forth in order to provide thorough understanding of one or more embodiments. It may be evident that such embodiments may be practiced without these specific details.

is a block diagram of a process control plantof a process plant, according to an embodiment of the present disclosure. The process control plantcomprises operating reactor unitand a control systemfor operating the operating reactor units. The operating reactor unitcomprises an enclosureand inlet and outlet jacket. The operating reactor unitis a counter current heat exchanger, for example. The enclosureis capable of yielding a solid product from a solution through a crystallization process. The enclosurecomprises a crystallization massand a mass temperature sensor. The crystallization massis a hot fluid. The crystallization mass temperature can be single or multi-point smart digital RTD temperature sensor. The mass temperature sensoris capable of periodically measuring temperature values of the crystallization mass, referred as crystallization mass temperature throughout the specification document. The mass temperature sensoris also capable of transmitting the measured temperature values of the crystallization massto the control system. The inlet and outlet jacketcarry a utility, which may be a cold fluid.

The process control plantfurther comprises one or more external temperature sensorsA-B for measuring utility jacket inletA temperature and utility jacket outlet temperatureB and steam inlet temperature. The external temperature sensorsA-B periodically measures and provides temperature inputs to the control systemduring operation of the operating reactor unit.

The process control plantfurther comprises one or more flow metersfor measuring one or more utility flow rate with respect to the one or more operating reactor unitand measuring steam flow rate. The one or more flow metersmay be an electromagnet flow meter. The one or more flow metersis capable for capturing utility management, properties of utilities, and parameters related to utility flow management. The utility flow management comprises managing desired utility at desired temperature, at desired time, and at desired flow. Specifically, utility flow management refers to selection of right utility temperature at right time with desired flow. This is based upon identifying a pinch temperature. This is achieved, firstly, when the reactors unitsare designed, pinch temperature value is defined for a given cooling surface area (A) and overall heat transfer coefficient (U). This pinch temperature value is monitored and when the pinch temperature value is met with 80% of final control element opening, then the automatic control valvesA-B with smart positionersA-B are repositioned such as to switch over to next utility. With this, the cooling efficiency of the operating reactor unitmay also be monitored. With increase in the pinch temperature value, the efficiency deteriorates. The reason could be scaling or fouling. This could be tracked efficiently. Further, temperature of utility is controlled by ratio controller by mixing hot and cold fluid. The properties of utilities comprise heat balance during supply of utility, changeover with air purging and admitting new utility.

Further, the process control plantcomprises one or more automatic control valvesA-B comprising a smart positionerA-B for positioning a control element and controlling flow of utility into the one or more operating reactor unit. The automatic control valveA-B is provided for controlling outflow of utilities (e.g.) from the operating reactor unit. The automatic control valveA-B e.g. pneumatically actuated full bore ball valve.

Further, the process control plantalso comprises on-off valvesA-N for air supply, jacket inlet, jacket recirculation, isolation of magnetic flow meter, steam condensate, vent, jacket outlet, steam isolation and the like.

The control systemis coupled to the one or more automatic control valvesA-B, one or more flow meters, the mass temperature sensorand the one or more external temperature sensorsA-B. the control systemis capable of managing the crystallization process in the process control plant. The control systemis capable of capturing process parameters of the one or more operating reactor unit. The process parameters are captured via the one or more flow meters, the mass temperature sensorand the one or more external temperature sensorsA-B. The process parameters comprises cooling rate, utility management, super saturation, temperature of the operating reactor unit, properties of utilities, parameters related to utility flow management, smart positioner properties, and the like and wherein the utility flow management comprises managing desired utility at desired temperature, at desired time, and at desired flow. Further, the control systemis capable of predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the one or more operating reactor unit. Furthermore, the control systemis capable of controlling process control loop associated with the one or more Operating reactor unitbased on the desired process parameters and the first set of parameters.

The control systemcomprises a control unitfor monitoring and controlling the process control loop associated with the one or more operating reactor unit. The control unitfurther comprises a process control module stored in the form of machine-readable instructions and executable by the processor. One can envision that the process control module may reside in an industrial cloud environment, wherein the control systemmay provide the inputs from the one or more sensing unitA-B,,and receive control signals for operating the reactor unitsfrom a cloud server in the industrial cloud environment. The detailed components of the control unitis depicted in. In an embodiment, the control unitmay include human machine interface, a control unit and the like.

The control systemfurther comprises a remote input/output boxfor transmitting control signals to the one or more flow meters, the mass temperature sensorand the one or more external temperature sensorsA-B. The remote input/output boxmay be connected to the control unitvia a network. Such networkmay include Ethernet connection. In an embodiment, the control systemis capable of analyzing the first set of parameters comprising information related to process dynamics and process disturbances associated with the one or more operating reactor unit. Further, the control systemis capable of periodically monitoring the process control loop associated with the one or more operating reactor unit. In the process control plant, the control systemis located in a safe area or in the same hazardous zone where the operating reactor unitare located.

In an exemplary operation, the operating reactor unitis used for cooling the crystallization massfrom utility which are fed in the enclosure. Once batch cycle is started, the process parameters are periodically captured and monitored by the control system. Once, there is a deviation observed in the actual process parameters which are captured and desired process parameters, then appropriate control signals are generated and transmitted in a desired sequence to the flow meters, automatic control valvesA-B, the smart positionersA-B and the on-off valvesA-B to control the process control loop and ensure smooth phase of crystallization process at the operating reactor unit. During generation of control signals, various other parameters such as first set of parameters, second set of parameters and third set of parameters are considered to attain better control the rate of nucleation and crystal growth in crystallization process.

In various embodiments, the process control plantcan be part of a distributed control system employed in a process plant. The process control plantcan be used for different combination of utilities and crystallization massfor different volumes at different times without performing re-calibration. Thus, same operating reactor unitcan be used for multiple batches. Also, the process control plantcan seamlessly operate one or more operating reactor units using a single control system. Additionally, the process control plantimproves heat balance during supply of utility, changeover with air purging and admitting new utility. Advanced temperature control help to operate reactor unitin narrow metastable zone. This means controlled nucleation begins, and also the polymorphs are avoided. Also, the process control plantcan operate in co-ordination with existing PID controller to provide better rate of cooling control thereby providing measurable improvement in process parameters. This further results in reduced batch time as no additional milling operation is required. Further, the process control plantensures consistent process point and reduced human intervention ensuring safe operation of the process control plant.

Further, as solid (for e.g., crystallization mass) is precipitating out, energy is released to surrounding environment. Hence, crystallization is exothermic process. If the nucleation rate of the crystallization massincreases, more amount energy is released. This raises the temperature of crystallization mass. This means cooling rate needs to be decreased. The process control plantconsiders measuring temperature of crystallization mass, jacket inlet and outlet temperatures of utilities at a time frequency pre-determined, settable. This ensures the cooling rate is adopted as per the process demand. This also ensures the nucleation is controlled in a better way. The process control plantis thus predictive by using knowledge of chemistry, physics and automation. Hence, the process control plantmonitors, analyzes and controls the crystallization process such that chances for occurrence if any error or faults are decreased. Moreover, the process control plantallows the control systemto decides action for utility requirement for heating and cooling. The control systemdecides when to use traditional PID controller mode and when to use auto mode.

Althoughillustrates the process control plantwith a single operating reactor unitconnected to the control system, one can envision that multiple such operating reactor units can be coupled to the control systemand a process control plantvia the Input/output modules, and the control systemcan operate multiple such reactor units simultaneously.

is a block diagram of a control unitas shown in, according to an embodiment of the present disclosure. The control unit (CCC)comprises a processor, a memory, a communication module, a network interface, an input/output moduleand a bus. The CCCis capable of monitoring and controlling the crystallization process in the process control plant. Specifically, the CCCis capable of predicting desired process parameters based on first set of parameters and the captured process parameters and controlling process control loop associated with the operating reactor unitbased on the desired process parameters and the first set of parameters.

The processor, as used herein, means any type of computational circuit, such as, but not limited to, a microprocessor, a microcontroller, a complex instruction set computing microprocessor, a reduced instruction set computing microprocessor, a very long instruction word microprocessor, an explicitly parallel instruction computing microprocessor, a graphics processor, a digital signal processor, or any other type of processing circuit. The processormay also include embedded controllers, such as generic or programmable logic devices or arrays, application specific integrated circuits, single-chip computers, and the like.

The memorymay be volatile memory and non-volatile memory. A variety of computer-readable storage media may be stored in and accessed from the memory. The memorymay include any suitable elements for storing data and machine-readable instructions, such as read only memory, random access memory, erasable programmable read only memory, electrically erasable programmable read only memory, hard drive, removable media drive for handling compact disks, digital video disks, diskettes, magnetic tape cartridges, memory cards, and the like. As depicted, the memoryincludes a process control module. The process control moduleis stored in the form of machine-readable instructions on any of the above-mentioned storage media and may be executed by the processor. When executed by the processor, the process control moduleis capable of capturing process parameters of the operating reactor unitin the process plant. The process parameters are captured via the one or more sensing unitA-B,,. The process control moduleis further capable of predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the operating reactor unit. Furthermore, the process control moduleis capable of controlling process control loop associated with the operating reactor unitbased on the desired process parameters and the first set of parameters.

The communication modulemay enable communication of the CCCwith the one or more sensing unitA-B,,, and the one or more automatic control valvesA-N and the operating reactor unitvia input/output modules. For example, the communication modulemay periodically receive inputs from the one or more sensing unitA-B,,. The inputs may indicate process parameters. Also, the inputs may indicate whether the crystallization process is in control or not. The communication modulemay enable transmit control signals to the automatic control valvesA-B for operating the automatic control valvesA-B.

The network interfacehelps in managing network communications between the CCCand the one or more sensing unitA-B,,, the one or more automatic control valvesA-B, and the operating reactor unit.

The input/output unitmay be a human-machine interface Which enables operator to view process data associated with the operating reactor unitand control process associated with the operating reactor unit. It can be noted that, the CCCmay have integrated human-machine interface or a human-machine interface externally coupled to the CCC.

is a block diagram of a process control moduleas shown in, according to an embodiment of the present disclosure. In, the process control modulecomprises data receiver module, data analyzer module, process parameter prediction module, controlling module, mode selection module, crystallization process monitoring module, a database, and a data visualizer.

The data receiver moduleis configured for capturing process parameters of an operating reactor unitin the process plant. The process parameters are captured via one or more sensing unitA-B,,. The process parameters comprise cooling rate, utility management, super saturation, temperature of the operating reactor unit, properties of utilities, parameters related to utility flow management, smart positioner properties, and the like. The utility flow management comprises managing desired utility at desired temperature, at desired time, and at desired flow. The one or more sensing unitA-B,,comprises one or more temperature sensorsA-B external to the operating reactor unitfor measuring utility jacket inletA temperature and jacket outletB temperature, one or more temperature sensordeployed internal to the operating reactor unitfor measuring crystallization mass temperature, one or more flow metersfor measuring utility flow rate, a smart positionerA-B with an automatic control valveA-B for positioning a control element and controlling flow of utility into the operating reactor unit.

In an embodiment, the one or more sensing unitA-B,,captures the process parameters and transmits the process parameters to the data receiver module. The data receiver modulereceives the process parameters and parses the process parameters for data integrity. Further, the data receiver modulemay capture any other data relevant to any hardware component involved in the crystallization process.